The CTSI provides pilot funding for innovative translational research and the development of research methods at BU. That encompasses the continuum from development of new therapies and diagnostic tests, to studies of the population health impact of health interventions.
The overarching goal of the BU CTSI Pilot Grant Program is to help investigators explore and solve major challenges in translational science, especially those that address the special health problems of our urban communities, by developing and deploying new tools, methods and processes to expedite clinical and translational research and discovery.
We seek to stimulate individual and team science in all areas of translational research related to the prevention, diagnosis, and management of human disease. We welcome researchers engaged in translational basic/bench, clinical, biomedical, patient-oriented, implementation, and population health science.
REQUEST FOR APPLICATIONS INTEGRATED PILOT GRANT PROGRAM ANNOUNCEMENT
2020 – 2021 CYCLE
Release Date: September 1, 2020
Application due date: November 1, 2020, at 5 PM EST
Funding Announcement: Spring, 2021
Earliest Activation Date: April 1, 2021, or July 1, 2021 (for DOM funded awards)
This RFA is open to ALL members of the BMC/BU community and represents a collaborative effort between the CTSI and partner organizations to fund meritorious research applicable to at least one (or more) of the components noted below: 1. CTSI General Funds 2. Community-Engaged Research 3. Bioinformatics/Mobile Health 4. BU School of Medicine (BUSM) 5. Henry M. Goldman School of Dental Medicine (GSDM) 6. Evans Center for Biomedical Research 7. Department of Medicine (DOM) 8. Addiction Science Research 9. This component funds applications with research objectives consistent with the mission of Boston Medical Center Applicants must have a primary faculty appointment at Boston University, and the research to be conducted must be based at Boston University, Boston Medical Center, or any of their affiliated hospitals and health centers. Faculty with co-appointments at BU and affiliated institutions are also encouraged to apply. Please see above for additional eligibility requirements based on the component to which the applicant is applying. In particular, we encourage early investigators to apply. Including those with institutional or individual mentored research awards from NIH or Foundations. Recipients of previous CTSI awards are eligible to apply for awards to support new research projects, providing awards are at least two years apart. Individuals from under-represented groups are highly encouraged to apply. Applications from teams of investigators particularly that cross disciplines, Departments and Schools Institutions are highly encouraged. BU collaborations are strongly encouraged-if your project involves an outside collaborator, provide justification as part of your application. If you are looking for BU collaborators, please go to BU Profiles or send a request to the BU CTSI Navigator team at ctsisvcs@bu.edu . Two award levels are offered: The level of funding awarded to successful applicants will be determined after a review of the budget request and budget justification. Funds may be used for any purpose to support the proposed research. Typical expenses include: Funds may not be allocated to PI or Co-I salary. Awards are not transferable to any other institution (sub-awards are not allowed). Pilot grants are not intended to supplement existing funded awards. Significant overlap in Pilot grant Aims with Aims from a funded grant must be disclosed and justified at the time of submission. Research Proposed in response to this RFA must be accomplished within the specified award period. IRB and IACUC Approvals: All IRB and IACUC protocols must be approved prior to the expenditure of any funds. Delayed Onset Human Subjects Research: The NIH requires that the CTSI obtain explicit approval from the NIH for any CTSI funded pilot with research involving human subjects. Accordingly, the IRB-approved protocol and other materials must be submitted to the NIH at least 45 days prior to the project start date. CTSI personnel will work with awardees to meet these requirements for those pilots that are funded with CTSI grant funds. Prior Approval of Vertebrate Animals Research: We strongly advise all Pilot grantees to begin the IRB/IACUC approval process at the time of final grant submission. If you are selected for funding, you will be required to provide your IRB/IACUC approval before funds are released to you. If at the time of notice of award, you have not submitted your IRB/IACUC application, you will be required to meet with a CTSI IRB/IACUC consultant within 2 weeks and expected to follow a strict timeline for regulatory submission. An award may be rescinded for failure to secure IRB/IACUC approval 3 months after notice of award. All applications can be submitted here and must include: Applications will be reviewed by the BU CTSI Scientific Review Committees comprised of faculty with relevant expertise analogous to the NIH review process (with focus on Significance, Innovation, Approach, and Investigators). Specific review criteria include, but are not limited to: New this cycle – Awarded investigators will be required to present a brief synopsis of their project progress to a panel of CTSI and institutional leaders that will be recorded for dissemination. Applicants will be expected to present for 10 minutes followed by 5 minutes of Q&A. The date of the presentation symposium will occur at the end of the grant award year (ie, in Spring 2022 for this award cycle).Priority Areas of this RFA
Any CRC or BMC/BUMC faculty member may apply to this component. While all areas of investigation are eligible, the CTSI is particularly interested in supporting research that involves special populations served by BMC/BUMC including (but not limited to) children and adolescents; the elderly; underserved and low socioeconomic status (SES) patients; as well as and diseases that affect patients across their lifespan.
Any CRC or BMC/BUMC faculty member may apply to this component. These projects must be designed to stimulate community-academic partnerships with the goal of catalyzing innovative translational research that is responsive to community health needs. We define community as the diverse, under-resourced populations served by Boston Medical Center and its affiliated community health centers.
Any CRC or BMC/BUMC faculty member may apply to this component. These projects must leverage existing bioinformatics resources or mobile health applications to facilitate improved health outcomes, facilitate access to care, or address health disparities among vulnerable populations.
Faculty whose grants are submitted though BUSM (BU Office of Sponsored Programs) are eligible to apply for this funding element. For all projects submitted in this area, there is a preference for coordinated applications from multiple investigators. “Applications related to research in breast & prostate cancer, sexual medicine, neuroscience, and collaborations with Chinese universities (not Taiwan) are strongly encouraged. Applications for up to $50K will be considered.
This funding element specifically funds meritorious applications from GSDM faculty.
The CTSI will support new research programs that align with existing Affinity Research Collaboratives (ARCs) projects supported through the Evans Center for Interdisciplinary Biomedical Research (http://www.bumc.bu.edu/evanscenteribr). This element is intended to:
• Fund projects from non-ARC affiliated investigators that facilitate entry into an established Evans Center ARC
• Fund projects from current ARC investigators that expand a current ARC with an innovative direction
• Fund projects from any investigator that contributes to the development of a new ARC in the following year
Faculty members with primary appointments in the Department of Medicine are eligible to apply for this component. All meritorious applications will be considered across the T1-T4 spectrum.
Any CRC or BMC/BUMC faculty member may apply to this component. Addiction science is a principal research focus of CTSI as supported through partners like the BMC Grayken Center and SPH Alcohol Addiction Center. The CTSI is interested in supporting applications that leverage existing Grayken Center resources, SPH Alcohol Addiction Center resources, or explore new areas in the field of addiction science.
In specific, applications must be responsive to the following subject areas: (1) to define or innovate novel models of care, or (2) to discover effective ways to disseminate or implement existing evidence-based care models. Proposed projects should be relevant to the care of BMC’s patient population, and might include (but are not limited to) addiction services, prevention, health and racial equity, chronic illness management, social determinants of health, diseases that affect patients throughout their lifespan, or integrated behavioral health. Investigators should explain how their pilot proposals fit into the translational spectrum of research.Eligibility
Funding Levels
1. Direct costs up to $20,000 may be requested for applications with a single PI
2. Direct costs up to $50,000 may be requested for applications with 2 or more PI’s comprising a credible research team (CTSI general funds, BUSM and GSDM awards only)
Requirements for Regulatory Approval
The NIH requires that the CTSI obtain explicit approval from the NIH for any CTSI funded pilot with research involving vertebrate animals. IACUC approval documentation and other materials must be submitted to the NIH at least 45 days prior to the project start date. CTSI personnel will work with awardees to meet these requirements for those pilots that are funded with CTSI grant funds.
Application Submittal Process
• A clear translational focus, including a collaboration with a patient-oriented science research team
• Focus on diseases that disproportionately affecting the BU/BMC patient population or ages at the extremes of the lifespan (children and the elderly)
• Approved IRB or IACUC protocols that would permit initiation of research activities as soon as possible
Available Resources
Available Resources for the Pilot Grant Application
The CTSI offers an array of research resources in support of research at BU and we strongly encourage CTSI Pilot Grant applications to use these valuable resources. In many cases, leverage of these resources increases the competitiveness of an application. Some examples include the following:
- Regulatory Support
- Grant Writing & Editing, Formatting and Editing Services
- Biostatistics, Data Management & Analysis
- Research Tools
- Study Implementation
- Research Networking
- Consultations – CTSI staff will offer feedback on feasibility, impact, and design or the proposed scientific investigations
To request a CTSI free service please visit the CTSI Research Navigator Team page at here.
If funded, the awardee agrees to submit an online report after the end of the award term indicating key results and any publications, grant applications, funded awards that resulted from the project, new collaborations, and other outcomes. This report must be completed on time if a 2nd stage renewal application is being pursued. Additional abbreviated reports will be requested on an annual basis for 2 years following completion of funding. Any follow on funding depends on prompt and accurate progress reports. Awardees will be contacted regarding the report, once needed. Awardees must acknowledge the CTSI grant in any publication or presentation that arises from data collected through this CTSI funded award, the language provided below is recommended: “This publication [or project] was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Boston University Clinical & Translational Science Institute Grant Number 1UL1TR001430. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.” Awardees are expected to serve on future CTSI Pilot Grant Application Review panels and to provide feedback on the CTSI pilot program. They may be asked to participate in CTSI related symposia or other functions. Awardees may be matched with relevant CTSI functions to support regulatory requirements or completion of proposed Aims and are expected to follow through on suggested timeliness and meetings with CTSI staff. Failure to comply with all post-award requirements jeopardizes eligibility for future Pilot award funding. We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Direct your questions to:Post Award Requirements
Where to Direct Inquiries
Frederick L. Ruberg, MD
Section of Cardiovascular Medicine, Department of Medicine
Director, Pilot Grant Programs,
Boston University Clinical and Translational Science Institute
Boston University School of Medicine
frruberg@bu.eduAdministrative Contact:
Hubert Wong
Assistant Director,
Boston University Clinical and Translational Science Institute
617.358.7553
ctsipilots@bu.edu
2020 Integrated Pilot Grant Awardees
Peer Recovery Coaching for HCV and Opioid Use Disorder Treatment
The U.S. opioid epidemic is associated with a surge in hepatitis C virus (HCV) infections among persons who inject drugs. Despite the availability of curative therapy, treatment uptake remains low in this group. The goal of this study is to determine the feasibility and acceptability of a peer intervention to improve linkage to HCV care, treatment initiation, and cure among individuals with a history of opioid use disorder. Our findings will serve as pilot data for a planned NIH R01 proposal.
Sabrina A. Assoumou, MD, MPH, is Assistant Professor of Medicine at Boston University School of Medicine and an attending physician in the section of Infectious Diseases at Boston Medical Center. She is a clinician-investigator who provides care to human immunodeficiency virus (HIV)-infected patients at the BUSM/BMC’s Centers for Infectious Diseases. Her research focuses on medical complications of substance use including HIV and hepatitis C virus (HCV). She is also interested in models of care and improving the continuum of care for individuals with HIV/ HCV. She is currently the Principal Investigator on a NIH K23 Mentored Career Development Award to improve linkage to care after testing for HIV and HCV at a drug detoxification center.
Dr. Assoumou graduated magna cum laude from Williams College and obtained her medical degree from the University of Rochester School of Medicine and Dentistry. She then completed a combined Internal Medicine Pediatrics residency at Brown University and an Infectious Diseases Fellowship at Harvard University’s Beth Israel Deaconess Medical Center where she was awarded the Finland Award for Research Excellence. She also earned a Masters of Public Health at the Harvard T.H. Chan School of Public Health. Dr. Assoumou received an Excellence in Teaching Hospital-Based Faculty Award at BMC in 2017. She was also recognized as the Distinguished Faculty of the Month in April 2020 for her service to the BUSM community in teaching, activities on committees, and the mentoring of students, trainees and junior faculty.
Data Driven Youth Led Health Promotion Strategy for a Safety Net Accountable Care Organization
The “Data Driven Youth Led Health Promotion Strategy for a Safety Net Accountable Care Organization” is a partnership between researchers at the Boston University School of Social Work and Boston Medical Center’s Department of Family Medicine. The overall goal of the project is to develop and vet a youth driven health promotion campaign informed by a youth led health assessment. The research will be guided by a youth advisory board consisting of six to eight youth of color who will be trained in the principles of youth participatory action research (YPAR), health equity, the social determinants of health, health promotion practice, and data driven planning.
Astraea Augsberger is an Assistant Professor at Boston University School of Social Work. She earned her MSW and Ph.D. from Columbia University. She has over a decade of clinical practice experience with children, youth and families in the child welfare, juvenile justice and mental health systems. Her research interests include youth civic engagement, youth development, child welfare policy and programs, and health equity. She employs community engaged research, youth participatory action research, and in-depth qualitative research methods to elevate the voices of youth and communities in identifying research priorities and relevant solutions to community concerns. She is an affiliated faculty member of the Boston University Center for Innovation in Social Work & Health (CISWH) and the Boston University Initiative on Cities (IOC).
Dr. Katherine Gergen Barnett is the Vice Chair of Primary Care Innovation & Transformation and the Program Director in the Department of Family Medicine at Boston Medical Center (BMC). Katherine joined BMC in 2009 after completing her residency and chief residency there. Prior to BMC, Dr. Gergen Barnett attended Yale University School of Medicine, worked at NIH, and completed a fellowship studying a model of group prenatal care for underserved women.
Dr. Gergen Barnett’s primary interests are behavioral health integration, preventive medicine, nutrition, mindfulness-based stress reduction, women’s health, and group care. Dr. Gergen Barnett’s research career has been primarily focused on innovative models of care to address chronic medical conditions, physician burnout, and engaging community partners in creating feasible solutions to increase health and wellness in urban communities.
“Immune Response and mEdical Complications of coVid-19 suRvivors (I-RECOVR) study”
The Study will follow a cohort of recovered patients to evaluate if those who survive acute illness with COVID-19 are at risk for continued physical disabilities or new medical sequalae, and whether these presentations are determined by initial disease severity or patient characteristics. Additionally, the study will follow this cohort over a two-year period of time to determine if survivors of COVID-19 are at risk for reinfection with SARS-CoV-2 and evaluate if incidence of reinfection or medical sequelae after recovery are associated with nature and longevity of immune response. Dr. Bhadelia serves as the principal investigator of a prospective biorepository study supported by a grant from Massachusetts Coalition for Pathogen Readiness and through internal support from Boston Medical Center. Currently, the study, entitled “Natural History of COVID-19 Confirmed Cases at Boston Medical Center (IRB H40047),” includes the longitudinal follow up of 200 hospitalized COVID-19 patients. This study is in the process of being expanded to cover 100 ambulatory COVID-19 patients and the two- year follow up of 200 COVID-19 survivors. The prospective study collects basic demographic and medical information as well as biological samples for use by Boston Medical Center and Boston University researchers. I-RECOVER study is layered on top of the survivor arm of this study and this pilot grant will be used to conduct survey tools, in person interviews, and collect biological samples for analysis mentioned above. The pilot data generated from the early part of I-RECOVER project will be used to support an R01 grant that will fund virologic and immunologic analysis on the stored samples as well as more extensive imaging of survivors with continued medical sequelae.
Dr. Nahid Bhadelia is an infectious diseases physician and the Medical Director of Special Pathogens Unit at Boston University School of Medicine, a medical unit designed to care for patients with highly communicable diseases. She is an Associate Professor in the Section of Infectious Diseases. She oversees the medical response program for Boston University’s maximum containment Biosafety Level 4 program at National Emerging Infectious Diseases Laboratories.
During the West African Ebola epidemic, she served as a clinician in several Ebola treatment units, working with World Health Organization and Partners in Health. She currently serves as the clinical lead for the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) program which is a joint US-Ugandan effort to create clinical research capacity to combat viral hemorrhagic fevers in Uganda at the border of Democratic Republic of Congo. She serves on national and interagency groups focused on medical countermeasures, the intersection between public health preparedness, research, and clinical care for emerging pathogens. Her research focuses on identification of safe and effective clinical interventions and infection control measures related to viral hemorrhagic fevers.
She has served as a subject matter expert to US Centers for Disease Control and Prevention, Department of Defense, Global Fund to Fight AIDS, Tuberculosis and Malaria, and World Bank.
Dr. Bhadelia is also an Assistant Professor at the Institute of Human Security at the Tufts Fletcher School of Law and Diplomacy, where she teaches a course on human security and emerging infectious diseases. She received her Doctorate of Medicine from Tufts University and completed her internal medicine residency and chief residency at Mount Sinai Hospital in New York. Her Infectious Diseases Fellowship was completed at Columbia Presbyterian Hospital.
PTH/PTHrP Receptor Signaling in Osteocytes during Aging
Dr. Divieti Pajevic’s research is focused on studying the effects of hormones, such as parathyroid hormone, and mechanical forces on bone and teeth. Recently, her group has been investigating the cross-talk between bone and muscle and the effects of aging. In her current CTSI proposal titled “PTH/PTHrP Receptor Signaling in Osteocytes During Aging,” Dr. Divieti Pajevic will use a combination of genetically modified mice and cell lines to investigate if PTH signaling in osteocytes alters skeletal progenitors and protects these cells from senescence.
Paola Divieti Pajevic, MD, PhD, is an Associate Professor of Translational Dental Medicine at the Goldman School of Dental Medicine at Boston University and the Director of the Bone Cells Core which is part of the MGH-Center for Skeletal Research.
Lionoleic Acid Promotes Pathogenic T Cells in Type 1 Diabetes
Type 1 Diabetes is an autoimmune disease caused by T cells that destroy the insulin-producing beta-cells in the pancreas. The incidence of Type 1 Diabetes is rapidly rising worldwide due to currently unknown environmental factors that promote the autoimmune response in genetically susceptible individuals. There is growing evidence that specific metabolites derived from the diet or microbiome have the capacity to influence the functions of T cells and may promote pathogenic T cells in autoimmune diseases. We discovered that addition of the dietary fatty acid linoleic acid to in vitro T cell cultures altered the balance between pathogenic IL-21-producing and protective IL-10-producing T cell subsets in favor of the cells with pro-diabetic activities. The goals of this CTSI pilot grant are to test whether autoreactive T cells exposed to linoleic acid have an increased capacity to cause diabetes in vivo, and whether feeding diabetes-susceptible NOD mice a linoleic acid-rich diet will accelerate diabetes development. Our study has the potential to identify a dietary factor that is increasingly present in Western diets as a driver for increased Type 1 Diabetes susceptibility. This finding may form the basis to develop preventative dietary interventions in susceptible individuals and/or to target the metabolic and signaling pathways that underlie linoleic acid-based induction of diabetes-causing T cells.
Dr. Hans Dooms is an immunologist who currently holds a position as an Assistant Professor in Medicine and Microbiology at the Arthritis and Autoimmune Diseases Research Center of Boston University School of Medicine. He received his Ph.D. from Ghent University in Belgium and continued his training in immunology at the University of California San Francisco in the laboratory of Dr. Abul Abbas. His research interests are focused on the biology of T cells and their role in the autoimmune diseases Type 1 Diabetes and Systemic Sclerosis. His laboratory is currently studying how autoreactive T cells acquire and maintain their disease-causing properties and how these cells escape immune regulatory mechanisms aimed at preventing autoimmunity. Dr. Dooms has received funding for his research from NIH, JDRF, and the American Diabetes Association. He has authored 29 publications, many included in some of the most prestigious journals in the field of immunology.
Defining the Role of Hippo Pathway Inactivation in Melanomagenesis
Dr. Ganem’s CTSI award is focused on testing the hypothesis that inactivation of the Hippo tumor suppressor pathway plays an important role in melanoma development.
Neil J. Ganem is an Associate Professor in the Department of Pharmacology & Experimental Therapeutics, and Department of Medicine, Division of Hematology and Oncology. He directs the Laboratory of Cancer Cell Biology, where his team used a combination of high-resolution microscopy, genome-wide screening, bioinformatics, and animal model systems to understand the causes and consequences of genome instability in human cancer.
Primary Care Connection in Maine
Millions of Americans have gained health insurance under the Affordable Care Act’s Medicaid expansion. However, health insurance is only a first step toward the goal of improving population health; receipt of primary care is a critical follow-up step. Despite the array of known benefits of primary care, little empirical work has examined how states can encourage uptake of primary care among new Medicaid enrollees. To address this gap in the evidence, we propose to design and pilot test an intervention to increase engagement with primary care services among newly enrolled Medicaid beneficiaries in the state of Maine, in partnership with the Office of Member Services (OMS) at the Maine Department of Health and Human Services. The pilot study will be a single blinded, randomized, controlled trial of a behavioral intervention to increase the PCP visit rate within the first six months of new Medicaid enrollment. The treatment arm will receive a one to two page letter that encourages new enrollees to get a free checkup and recommends a single provider, located within 30 miles of the enrollee’s home address. Clinics will be notified of newly assigned patients and encouraged to reach out to schedule initial appointments. The control arm will receive the current MaineCare enrollee packet of 23-pages, including a comprehensive provider directory. We will assess acceptability and feasibility of our intervention to MaineCare members, providers, and our partners at OMS. If the pilot trial proves acceptable and feasible, we will plan to implement a larger scale trial within 6 months of the pilot’s end.
The research team for this project includes Anna Goldman, MD, MPA, MPH, of BUSM/BMC; Sarah Gordon, PhD, MPH, of BUSPH; and Benjamin Sommers, MD, PhD, of Harvard T.H. Chan School of Public Health.
Anna L. Goldman MD, MPA, MPH, is a general internist practicing primary care, and a health services researcher. Her research centers on the effects of insurance and payment policies on care access for the poor and undeserved. She focuses on the health insurance programs established by the Affordable Care Act, the Medicaid expansion and Marketplace insurance. She also investigates the effects of accountable care organizations (ACOs) in the Medicaid program on health care quality and access. She has a medical degree from Mount Sinai School of Medicine, a Master’s Degree in Public Health from the Harvard T.H. Chan School of Public Health,and a Master’s Degree in Public Affairs from Brown University. She completed an internal medicine residency at Cambridge Health Alliance.
Sarah Gordon is an Assistant Professor in the Department of Health Law, Policy, and Management at the Boston University School of Public Health. Her research is dedicated to studying coverage and access to care among low-income populations, with a particular emphasis on Medicaid policy. Her work seeks to understand how the fragmentation of the U.S. health insurance system impacts utilization, quality, and continuity of care. Dr. Gordon recent projects leverage state-level datasets, such as all payer claims databases, and quasi-experimental study designs to evaluate the effects of state-level policies. She received her doctorate in Health Services Research from the Brown University School of Public Health and a M.S. in Social and Behavioral Sciences from the Harvard T. H. Chan School of Public Health
A Tool to Identify PrEP Eligible Youth in Primary Care
Pediatricians are the most common provider of primary care for youth, and frequently provide care to individuals through their early-to-mid 20s. Thus, pediatric primary care offers an opportune setting for identifying youth who are eligible for pre-exposure prophylaxis (PrEP). To successfully identify PrEP-eligible youth, it is essential that pediatricians ask valid, developmentally appropriate screening questions that resonate with youth and elicit accurate information. The objective of this proposal is to conduct mixed methods, translational research to develop (Aim 1), and conduct a pilot study (Aim 2) of a HIV risk assessment tool that pediatricians can integrate into their current primary care practice to identify PrEP-eligible youth. Data from the pilot study will directly inform a subsequent clinical trial of a comprehensive PrEP service delivery model for pediatric primary care.
Scott Hadland is a pediatrician and addiction specialist at Boston Medical Center and Boston University School of Medicine. He holds triple board certification in General Pediatrics, Adolescent Medicine, and Addiction Medicine. Dr. Hadland’s clinical and research interests focus on adolescent and young adult substance use disorder prevention and treatment. In the proposed work, Dr. Hadland will extend his work into human immunodeficiency virus (HIV) prevention among youth, with a goal of enhancing pre-exposure prophylaxis (PrEP) delivery in pediatric primary care.
Influenza Induced Lymphangiogenesis
The overall objective of this proposal is to identify lymphatic-centered strategies to contain viral lung infections. To achieve this goal, the PIs use a mouse influenza model that allows for deciphering the functional therapeutic properties and origins of the markedly expanded pulmonary lymphatic system that the PIs found accompanies influenza. Based on preliminary data, the central hypothesis is that new lymphatic growth facilitates immunomodulatory events and alterations in lymphatic cell function that are central to virus containment. The PIs propose to use the CTSI pilot grant to perform a detailed transcriptional analysis of lymphatic cells as the lung responds to influenza.
The PIs driving this project are Dr. Matthew Jones and Dr. Alan Fine. Together, they have a successful history of collaboration on various projects, grants, and papers.
Dr. Matthew Jones is a lung molecular biologist with an extensive history of studying the lung’s response to infection. Dr. Jones also brings a deep knowledge of gene expression analytical methodology to this project.
Dr. Alan Fine is a practicing pulmonologist with broad experience in the treatment of lung disease. He has a long history of external funding that supports work aimed at understanding the fundamental biology of lung cells, lung development, and disease mechanisms.
Clinical Pipeline for Single Cell Profiling of Triple Negative Breast Cancer
The research for this CTSI pilot award will recruit, consent, and invite BMC patients with breast cancer to participate in translational research, by providing biopsy specimens for single-cell RNA sequencing to answer cutting-edge research questions on the behavior of tumor cells and the immune environment.
Dr. Naomi Ko is an Assistant Professor of Medicine at Boston University School of Medicine (BUSM) and a medical oncologist at Boston Medical Center (BMC). Her research is directed to understanding the root causes of cancer disparities, the disconnect between scientific discoveries in cancer treatment, and delivery of evidence-based treatment to vulnerable, racial/ethnic minority women with breast cancer. She is actively investigating how tumor biology, social, and treatment factors influence breast cancer outcomes in undeserved, diverse breast cancer populations.
Single-Cell Analysis of AL Amyloidosis Plasma Cells
Since starting at BUSM in 2018, Gareth has established a program to study the aberrant plasma cells that underlie AL amyloidosis, which is a rare but often fatal form of systemic amyloidosis. These plasma cells normally secrete antibodies as part of the adaptive immune system. Aberrant proliferation in bone marrow causes overproduction of antibodies and, in some cases, amyloidosis. Comparing the gene expression of these cells to that of healthy plasma cells and those from a related disease, multiple myeloma, should reveal specific vulnerabilities that can be targeted for therapy. The CTSI pilot grant will enable researchers from the Amyloidosis Center to measure single-cell gene expression profiles of primary cells isolated from patient bone marrow aspirates. This project brings together the clinical work of the BU Amyloidosis Center with the cutting-edge instrumentation in the Department of Medicine Single Cell Sequencing Core Facility. These experiments will enable larger-scale studies to identify therapeutic targets and prognostic markers that could help to optimize treatments and benefit patients.
Gareth Morgan is a Research Assistant Professor in the Section of Hematology and Medical Oncology at the Boston University School of Medicine, and a member of the BU Amyloidosis Center. Originally from the United Kingdom, Gareth completed his B.Sc. in Biochemistry from Imperial College, London. He received his Ph.D. from the University of Sheffield, where he worked with Professors Rosie Staniforth and Jon Waltho. Gareth worked as a postdoctoral research associate with Professor Sheena Radford at the University of Leeds, and then with Professor Jeff Kelly at the Scripps Research Institute in San Diego, CA. Throughout his career, Gareth has studied how proteins fold, misfold and aggregate. He is especially interested in understanding how cells and organisms manage and maintain their proteomes, and why these processes break down to cause systemic amyloidosis diseases, where accumulation of protein aggregates leads to progressive organ failure. A major research focus is on developing small molecule drugs that can prevent protein aggregation, which could benefit patients with these diseases.
Machine Learning Risk Stratification of Stroke in Patients with AF
We aim to develop a clinically-oriented risk prediction model of stroke in patients with non-valvular atrial fibrillation using novel, clinically-oriented machine learning methods and data from Boston Medical Center and the UK Biobank
Non-valvular atrial fibrillation (NVAF) is associated with a five-fold increased risk of stroke.1 The most widely used prediction scales to risk stratify patients include the CHADS22,CHA2DS2-VASc3, and Framingham Risk scales.1,4 These are commonly used to guide management decisions (anticoagulation or antiplatelet therapy) for primary or secondary stroke prevention. However, like many risk prediction scales, they assume that the addition of risk factors is cumulative and linear,5 which limits their discrimination (C statistics of 0.68-0.7 in large validated studies)6,7 and generalizability. Advances in machine learning (ML) methods allow us to model non-linear risk in large datasets, improving performance, making individualized risk stratification possible. Moreover, our group has developed a novel and interpretable tree-based ML method specifically tailored for clinical applications. Optimal classification trees (OCTs) is an ML method that improves accurate classification compared to traditional statistical methods, while allowing practitioners to easily identify risk factors that contribute to outcomes.8 Such interpretability resolves the “black-box” or opaque classification disadvantage intrinsic to using many ML techniques. Our group has used these methods to stratify patients at high risk for emergent surgery, to predict 10-year cardiovascular risk, and to make treatment recommendations in diabetic patients.5,9,10 ML methods have not yet been used to develop clinically-oriented risk prediction models in cerebrovascular diseases like stroke risk in patients with atrial fibrillation (AF). We propose an innovative approach using a variety of novel, OCT-based methods to improve personalized stroke risk stratification in patients with non-valvular AF. Improved risk stratification would profoundly impact the population’s cardiovascular health, as it can inform management for approximately 5.3 million Americans with AF.11
Charlene Ong, MD, MPHS, is an Assistant Professor of Neurology and Neurosurgery at Boston University, Visiting Assistant Professor at Harvard Medical School and Massachusetts Institute of Technology, and a clinical Neurointensive Care Physician at Boston Medical Center. She received her undergraduate degree at University of Pennsylvania, her MD at Columbia University and her Master’s in Population Health Sciences at Washington University School of Medicine. Her research focuses on data-driven tools that support clinical decision making and optimize outcome after acute brain injury. She has received foundational support from the American Brain Foundation, Philips-MIT, the Peter Paul Career Development Committee, and the Clinical and Translational Science Institute at Boston University. Her aim is to build a robust ICU data science program and follow a K-track path toward the eventual goal of becoming an independently funded researcher and recognized leader in the field of neurocritical care.
Soft Robotic Platform for Restoring Haptic Feedback in Robotic Surgery
Robotic surgery has improved minimally invasive surgical procedures and shortened learning curves for surgeons. However, during robot-assisted procedures, haptic feedback is not available to the surgeon, resulting in uncontrolled force application which can lead to intraoperative complications. Absent haptic feedback is reputed to be among the reasons that impede further spread of surgical robots.
The capability to sense and touch the anatomy realistically has the potential to increase safety and precision during robotic surgery, with better patient outcomes. In this proposal, we will focus on restoring haptic feedback in minimally invasive robotic surgery by developing a soft robotic platform consisting of a soft sensing unit, to monitor forces exerted during surgical tasks and transduce this information to a soft actuation unit, that will map tactile information back to the surgeon.
Sheila Russo is an Assistant Professor in the Department of Mechanical Engineering and the Division of Materials Science and Engineering at Boston University. Prof. Russo completed her Ph.D. degree at the BioRobotics Institute, Sant’Anna School of Advanced Studies, Italy. She completed her postdoctoral training at the Harvard John A. Paulson School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. She is the founder and director of the Material Robotics Laboratory at BU that aims at bridging the gap between material science and robotics, and focuses on design, mechanics, and manufacturing of novel multi-scale and multi-material biomedical robotic systems. Her research interests include medical and surgical robotics, soft robotics, sensing and actuation, meso- and micro-scale manufacturing techniques, and advanced materials.
Pre-Clinical Validation of Novel Gene Editing Approaches for Sickle Cell Disease
With the support of the CTSI pilot grant, Dr. Vanuytsel will further develop the sickle cell disease (SCD)-specific iPSC platform as a pre-clinical tool to validate the efficacy of novel therapeutic gene editing strategies across a diverse SCD patient population.
Although SCD patients all share the same point mutation in the beta globin gene, the surrounding genetic background determines the severity of their disease course and response to therapy. Currently, several gene editing strategies are being explored as potentially curative approaches in clinical and pre-clinical trials. While these developments are truly exciting, their safety and efficacy will require thorough validation across a variety of SCD backgrounds to make sure that an effective treatment can be assured for every patient. iPSCs present an unlimited source of material that can be differentiated into erythroblasts that capture the exact genetic background of a patient, and thus make an excellent screening tool that could help predict the safety and efficacy of a particular therapeutic approach in a given genetic background prior to engaging in costly and invasive treatments.
Kim Vanuytsel is a Research Assistant Professor in the Division of Hematology and Medical Oncology at Boston University School of Medicine and the Center for Regenerative Medicine (CReM). She obtained a PhD in Stem Cell and Molecular Medicine from the Katholieke Universiteit Leuven (KULeuven) in Belgium. As a postdoc in Dr. George J Murphy’s lab, she developed novel resources and tools to better understand and treat blood disorders. Her current research focuses on finding better solutions for sickle cell disease (SCD) patients by using patient-specific induced pluripotent stem cells (iPSCs) as a versatile platform to study the disease, screen for compounds that can ameliorate the condition, and explore potential curative gene editing approaches.